POS0049 CLINICAL AND RADIOGRAPHIC RESULTS OF TAPERING AND WITHDRAWING CSDMARDS VERSUS STABLE TREATMENT IN RHEUMATOID ARTHRITIS REMISSION: 3-YEAR RESULTS FROM A RANDOMIZED CONTROLLED TRIAL
Authors: K. Kjørholt, N. P. Sundlisæter, A. B. Aga, J. Sexton, I. Olsen, H. Fremstad, C. Spada, T. M. Madland, C. A. Høili, G. Bakland, Å. Lexberg, I. J. Widding Hansen, I. M. Hansen, H. Haukeland, M. K. A. Ljosa, E. Moholt, T. Uhlig, T. K. Kvien, D. Solomon, D. Van der Heijde, E. A. Haavardsholm, S. Lillegraven
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tapering of disease modifying antirheumatic drugs (DMARDs) to achieve drug-free remission is a goal for the growing group of rheumatoid arthritis (RA) patients in remission. However, the long-term effects of tapering or withdrawal of DMARDs remain unclear. <h3>Objectives</h3> To compare the 3-year clinical and radiographic outcomes of three conventional synthetic DMARD (csDMARD) treatment strategies (continued stable treatment, half-dose treatment and tapering to withdrawal) among patients in sustained RA remission. <h3>Methods</h3> ARCTIC REWIND was a randomized, multicenter, open-label, clinical trial enrolling 160 RA patients in sustained remission for ≥1 year on stable csDMARD therapy from 10 different Norwegian rheumatology departments.(1) At baseline, patients were randomized 2:1:1 to stable csDMARDs, half-dose csDMARDs, or half-dose csDMARDs for one year, followed by withdrawal of all csDMARDs ("tapering to withdrawal"). The primary endpoint was absence of disease activity flare over the 3-year study period. A flare was defined as a combination of disease activity score (DAS)&gt;1.6, an increase in DAS ≥0.6 units since the previous visit and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Full-dose csDMARD treatment was reinstated upon flare. Secondary endpoints included remission (DAS, ACR/EULAR Boolean) at 1, 2 and 3 years, and 3-year change in radiographic joint damage evaluated by van der Heijde-Sharp score (vdHSS). Data were analyzed using Kaplan-Meier, Mann-Whitney test, Cox and mixed effect logistic regression, with stratification or adjustment for study center. <h3>Results</h3> Of 156 patients who received the allocated treatment strategy, 139 patients completed 3-years follow-up without major protocol violation. Mean baseline methotrexate dose/week was 19.0 mg in the stable group, 19.4 mg in half-dose, and 19.5 mg in the withdrawal group, and mean DAS at baseline was 0.8 in all groups. During the 3-year study period, 80.1% remained flare-free in the stable csDMARD group, 59.5% in the half-dose and 40.8% in the withdrawal group (<b>Figure 1</b>), with corresponding adjusted hazard ratio (aHR) for flare of 2.7 (95% CI: 1.3 to 5.5) in the half-dose group and 4.1 (2.1 to 8.0) in the withdrawal group, compared to stable csDMARD. The aHR was 1.5 (0.8 to 3.0) in the withdrawal group compared to the half-dose group. For all groups, a majority were in remission at 1, 2 and 3 years <b>(Table 1</b>), with the only significant group difference for ACR/EULAR Boolean remission at 3 years, with risk difference for withdrawal vs stable dose -25% (-45 to -6). Mean/median change in vdHSS after 3 years were 0.3/0.0 in the stable group, 1.0/0.5 in the half-dose group, and 0.7/0.0 in the tapering to withdrawal group, with significant difference between the stable and half-dose group, p&lt;0.01. Sensitivity analyses in the full analysis population gave similar results. <h3>Conclusion</h3> These 3-year data show that 41% of patients in the tapering to withdrawal arm achieved long-term drug-free remission, indicating that this is a realistic option for some RA patients in sustained remission. The two tapering strategies were associated with an increased risk of flares compared to full-dose csDMARD, and the half-dose group had more radiographic change. However, there were no differences in DAS-remission at the end of the study period. Further research identifying prognostic factors for successful tapering is needed. <h3>Reference</h3> [1]Lillegraven S et al. JAMA 2021 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Kaja Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Joseph Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada Consultant of: Advisory board UCB November 2022, Tor Magne Madland Speakers bureau: Cellgene (2017), Novartis (2018), Boehringer (2022), Christian A. Høili: None declared, Gunnstein Bakland Consultant of: Consultant fee from UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Advisory board for UCB Pharma 2x in 2022, NovartisNorge 2017 and 2018, Abbot 2012, Maud-Kristine A Ljosa Consultant of: Advisory Board for Abbvie i 2022, Ellen Moholt: None declared, Till Uhlig Speakers bureau: Lilly, Galapagos, Pfizer, UCB, Consultant of: Lilly, Galapagos, Pfizer, UCB, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Daniel Solomon Grant/research support from: Abbvie, Amgen, CorEvitas, Moderna, and Janssen, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma Director of Imaging Rheumatology bv, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, Siri Lillegraven Grant/research support from: Boehringer Ingelheim.